AzTrials
AzTrials

Bladder Urothelial CarcinomaPhase 2NCT04216290

A Study of Chemotherapy and Radiation Therapy Compared to Chemotherapy and Radiation Therapy Plus MEDI4736 (Durvalumab) Immunotherapy for Bladder Cancer Which Has Spread to the Lymph Nodes, INSPIRE Trial

A Phase 2 study testing Biopsy of Bladder, Biospecimen Collection and Cisplatin in people with Bladder Urothelial Carcinoma and Stage III Bladder Cancer AJCC v8, run by National Cancer Institute (NCI) at 216 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase II trial studies the benefit of adding an immunotherapy drug called MEDI4736 (durvalumab) to standard chemotherapy and radiation therapy in treating bladder cancer which has spread to the lymph nodes. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy of Bladder, Biospecimen Collection and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
216 sitesUnited States
Study dates
17 Mar 2021to 19 May 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • STEP 1 (RANDOMIZATION) ELIGIBILITY CRITERIA:
  • Patient must be >= 18 years of age.
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of step 1 randomization.
  • Patient must have histologically proven pure or mixed urothelial cancer of the bladder.
  • NOTE: Small cell carcinoma is excluded, however other variant histologies are permitted provided a component of urothelial carcinoma is present.
  • Patient must have documented node-positive and non-metastatic disease (any T, any N, M0). Node positivity must have been defined prior to receiving any systemic chemotherapy or induction chemotherapy.
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  • Node positivity can fall into either of the following categories and will be defined by imaging and/or biopsy:
  • A lymph node >= 1.0 cm in short axis on imaging (i.e., CT or MRI or positron emission tomography [PET]/CT).
  • A lymph node that is < 1 cm on imaging with either a biopsy confirming involvement with cancer or high suspicion of cancer.
  • For patients who have received induction chemotherapy (any type of systemic chemotherapy) for node positive bladder cancer prior to enrollment, there must be no signs of disease progression (CR/partial response [PR] or stable disease [SD]) based on restaging imaging and cystoscopy, which consists of:
  • CT chest, abdomen, and pelvis obtained after completion of induction chemotherapy and within 8 weeks prior to step 1 randomization.
  • NOTE: MRI can be used instead of CT per treating physician discretion.
  • Cystoscopic evaluation and attempt to perform maximal transurethral resection of bladder tumor (TURBT) performed by the participating urologist after completion of induction chemotherapy and within 12 weeks prior to step 1 randomization. If maximal TURBT is not possible for medical reasons, the enrollment must be discussed and approved with the study chair. Documentation of correspondences with the study chair must be kept on file.
  • Patients who achieve CR upon cystoscopy per urologist with no visible tumor (i.e., no need for additional TURBT), are allowed to proceed in the study as adequate resection with no residual disease in bladder.
  • For patients who have did not receive induction chemotherapy (any type of systemic chemotherapy) for node positive bladder cancer prior to enrollment, the following must be obtained:
  • CT chest, abdomen, and pelvis completed within 8 weeks prior to step 1 randomization.
  • NOTE: MRI can be used instead of CT per treating physician discretion.
  • Cystoscopic evaluation and attempt to perform maximal TURBT performed by the participating urologist within 12 weeks prior to step 1 randomization. If maximal TURBT is not possible for medical reasons, the enrollment must be discussed and approved with the study chair. Documentation of correspondences with the study chair must be kept on file.
  • For patients who may need repeat TURBT if their old TURBT has fallen out of window: If urologist determine no visible tumor (i.e., no need for additional resection) upon cystoscopy, they are allowed to proceed in the study as complete resection.
  • Patient must not have received any previous radiation therapy to the pelvic area.
  • Patient must agree to undergo CT simulation and treatment planning. If this is the first case registered at the site, then a pre-treatment radiation therapy (RT) review will be required and will take up to 3 business days. The patient cannot start radiation treatment prior to successful completion of this pre-treatment review. Therefore, careful planning is necessary to meet the deadline of starting radiation within 20 business days of step 1 randomization.
  • Patient must not have presence of concomitant active upper tract tumors or urethra tumors. History of previously adequately treated non-muscle invasive bladder cancer (NMIBC) are eligible. Previously treated urothelial cancer or histological variant at any site outside of the urinary bladder are allowed, provided they have been Ta/T1/carcinoma in situ (CIS) and post treatment follow up imaging and endoscopic evaluation shows no evidence of disease.
  • Patients with previous exposure to immune checkpoint inhibitor for non-muscle invasive disease are eligible. If given for NMIBC, the last dose must have been completed > 12 months prior to step 1 randomization.
  • Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.
  • All patients of childbearing potential must have a blood test or urine study within 14 days prior to step 1 randomization to rule out pregnancy.
  • A patient of childbearing potential is defined as any patient, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
  • Patients must not expect to conceive or father children by using accepted and effected method(s) of contraception or by abstaining from sexual intercourse from the time of step 1 randomization for the duration of their participation in the study and continue for at least 3 months after the last dose of protocol treatment.
  • Leukocytes >= 3,000/mcL (obtained < 14 days prior to step 1 randomization).
  • Absolute neutrophil count (ANC) >= 1,500/mcL (obtained < 14 days prior to step 1 randomization).
  • Hemoglobin >= 9 g/dL (obtained < 14 days prior to step 1 randomization).
  • Platelets >= 100,000/mcL (obtained < 14 days prior to step 1 randomization).
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (obtained < 14 days prior to step 1 randomization).
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained < 14 days prior to step 1 randomization).
  • Adequate renal function as evidenced by calculated (Cockcroft's formula) creatinine clearance or 24 hours actual creatinine clearance >= 30mL/min. The creatinine used to calculate the clearance result must have been obtained within 14 days prior to step 1 randomization. Actual body weight, not ideal body weight, must be used in the calculation.
  • Patients with human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months of step 1 randomization are eligible for this trial.
  • For patients with autoimmune conditions, patient must not have history of prior documented autoimmune disease within 2 years prior to step 1 randomization.
  • NOTE: Patient with vitiligo, Grave's disease, eczema or psoriasis (not requiring systemic treatment within 2 years prior to step 1 randomization) are not excluded. Patients with history of completely resolved childhood asthma or atopy are not excluded. Patients with asthma not requiring more than 10 mg/d or equivalent of prednisone are not excluded. Patients with well-controlled hypothyroidism on thyroxine replacement will be eligible as well. Patients with known history of hypoadrenalism on maintenance steroids will be eligible. Patients with type I diabetes mellitus will be eligible, provided their disease is well controlled. History of autoimmune related alopecia is also not an exclusion criteria.
  • Patient with active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) are not eligible.
  • Patient with a history of and/or confirmed pneumonitis are not eligible.
  • Patient with a history of primary immunodeficiency are not eligible.
  • Patient with history of allogeneic organ transplant are not eligible.
  • Patient must not have an active infection, including:
  • Tuberculosis (based on clinical evaluation that includes clinical history, physical examination, and radiographic findings, and tuberculosis testing in line with local practice).
  • Hepatitis B (known positive hepatitis B virus [HBV] surface antigen [HBsAg] result). Past or resolved HBV infection (defined as the presence of hepatitis b core antibody [anti-HBc] and absence of HBsAg) are eligible.
  • Hepatitis C. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction test is negative for HCV ribonucleic acid (RNA).
  • Patient must not have clinically significant liver disease that precludes patient from treatment regimens prescribed on the study (including, but not limited to, active viral, alcoholic or other autoimmune hepatitis, cirrhosis or inherited liver disease).
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Site is encouraged to discuss with the study chair if needed prior to enrollment.
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class IIB or better.
  • Patient must not have received live attenuated vaccine within 30 days prior to the first dose of durvalumab
  • NOTE: Patient, if enrolled, must not receive live vaccine whilst receiving durvalumab and up to 30 days after the last dose of durvalumab.
  • NOTE: Patient is permitted to receive inactivated vaccines and any non-live vaccines including those for the seasonal influenza and coronavirus disease 2019 (COVID-19) (Note: intranasal influenza vaccines, such as Flu-Mist (registered trademark) are live attenuated vaccines and are not allowed). If possible, it is recommended to separate study drug administration from vaccine administration by about a week (primarily in order to minimize an overlap of adverse events).
  • Patient must not have current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection).
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Patient must not have any unresolved toxicity (National Cancer Institute [NCI] CTCAE grade >= 2) from previous anti-cancer therapy with the exception of alopecia, vitiligo, and the laboratory values.
  • NOTE: Patients with grade >= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study chair.
  • NOTE: Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the study chair. Documentation of correspondences with the study chair must be kept on file.
  • STEP 2 (REGISTRACTION: ADJUVANT DURVALUMAB VERSUS [VS] OBSERVATION) ELIGIBILITY CRITERIA:
  • Patient must have evaluation to determine clinical outcome post step 1 treatment (chemoRT+/- durvalumab) with imaging (CT chest, abdomen, and pelvis) (preferably contrast with urogram, if not contraindicated) and cystoscopy with biopsy confirmation to ensure no progression and absence of >= T2 disease in the bladder. Patient should be registered to step 2 within 28 days from the determination of primary response to step 1 treatment. However, for patients previously on Arm C, an additional 4 week delay to step 2 registration is allowed.
  • Patient on the chemoRT+ durvalumab (Arm C) must meet the following:
  • Patient must have achieved either complete clinical response OR have demonstrated clinical benefit prior to continuing onto adjuvant durvalumab.
  • Patients who are to go on the adjuvant durvalumab (Arm E) must have recovered to at least grade 2 or less immune related adverse event (AE) prior to starting treatment except for immune related alopecia, clinically asymptomatic endocrinopathies. For patients who may have gotten immune related AEs during chemoRT+ durvalumab (Arm C), step 2 registration could be delayed up to additional 4 weeks to ensure recovery to at least grade 2 or lower prior to starting adjuvant therapy. However patients with durvalumab related AEs that require permanent discontinuation of durvalumab will not continue on the adjuvant treatment regardless of the response.
  • Patient must not have experienced immune related neurological disorder described as Guillain-Barré syndrome, myasthenic syndrome or myasthenia gravis, or meningoencephalitis during chemoRT+ durvalumab treatment.
  • Patient must not have experienced immune related myocarditis or immune related pericarditis during chemoRT+ durvalumab treatment.
  • ANC >= 1,000 mcL (must be obtained < 28 days prior to step 2 registration).
  • Hemoglobin >= 8g/dL (must be obtained < 28 days prior to step 2 registration).
  • Platelets >= 70,000 mcL (must be obtained < 28 days prior to step 2 registration).
  • NOTE: If recovery is not achieved, blood counts could be repeated weekly and step 2 registration could be delayed up to additional 4 weeks.
  • Patient on the chemoRT arm (Arm D) must have achieved either complete clinical response OR have demonstrated clinical benefit prior to be placed on the observation alone arm (Arm F).

Who cannot join

None listed.

Trial locations and contacts

216 sites in 1 country.

216 sites in 1 country

United States216 sites

  • Providence Regional Cancer System-Aberdeen

    Aberdeen, Washington, 98520

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • Mary Greeley Medical Center

    Ames, Iowa, 50010

  • McFarland Clinic - Ames

    Ames, Iowa, 50010

  • Anchorage Associates in Radiation Medicine

    Anchorage, Alaska, 98508

  • Alaska Breast Care and Surgery LLC

    Anchorage, Alaska, 99508

  • Alaska Oncology and Hematology LLC

    Anchorage, Alaska, 99508

  • Alaska Women's Cancer Care

    Anchorage, Alaska, 99508

  • Anchorage Oncology Centre

    Anchorage, Alaska, 99508

  • Katmai Oncology Group

    Anchorage, Alaska, 99508

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor

    Ann Arbor, Michigan, 48106

  • Duluth Clinic Ashland

    Ashland, Wisconsin, 54806

  • Northwest Wisconsin Cancer Center

    Ashland, Wisconsin, 54806

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • Mercy Oncology and Hematology - Clayton-Clarkson

    Ballwin, Missouri, 63011

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • PeaceHealth Saint Joseph Medical Center

    Bellingham, Washington, 98225

  • Saint Charles Health System

    Bend, Oregon, 97701

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • Illinois CancerCare-Bloomington

    Bloomington, Illinois, 61704

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Bozeman Health Deaconess Hospital

    Bozeman, Montana, 59715

  • Essentia Health Saint Joseph's Medical Center

    Brainerd, Minnesota, 56401

  • Lafayette Family Cancer Center-EMMC

    Brewer, Maine, 04412

  • Trinity Health IHA Medical Group Hematology Oncology - Brighton

    Brighton, Michigan, 48114

  • Trinity Health Medical Center - Brighton

    Brighton, Michigan, 48114

  • Saint Joseph Regional Cancer Center

    Bryan, Texas, 77802

  • Providence Saint Joseph Medical Center/Disney Family Cancer Center

    Burbank, California, 91505

  • Highline Medical Center-Main Campus

    Burien, Washington, 98166

  • Saint Alphonsus Cancer Care Center-Caldwell

    Caldwell, Idaho, 83605

  • Illinois CancerCare-Canton

    Canton, Illinois, 61520

  • Trinity Health IHA Medical Group Hematology Oncology - Canton

    Canton, Michigan, 48188

  • Trinity Health Medical Center - Canton

    Canton, Michigan, 48188

  • Mercy Cancer Center - Cape Girardeau

    Cape Girardeau, Missouri, 63703

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Memorial Hospital of Carbondale

    Carbondale, Illinois, 62902

  • SIH Cancer Institute

    Carterville, Illinois, 62918

  • Illinois CancerCare-Carthage

    Carthage, Illinois, 62321

  • Centralia Oncology Clinic

    Centralia, Illinois, 62801

  • Providence Regional Cancer System-Centralia

    Centralia, Washington, 98531

  • Christiana Care Health System-Concord Health Center

    Chadds Ford, Pennsylvania, 19317

  • Chelsea Hospital

    Chelsea, Michigan, 48118

  • Northwestern University

    Chicago, Illinois, 60611

  • Good Samaritan Hospital - Cincinnati

    Cincinnati, Ohio, 45220

  • Bethesda North Hospital

    Cincinnati, Ohio, 45242

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Clackamas Radiation Oncology Center

    Clackamas, Oregon, 97015

  • Providence Cancer Institute Clackamas Clinic

    Clackamas, Oregon, 97015

  • Mercy Cancer Center-West Lakes

    Clive, Iowa, 50325

  • UI Health Care Mission Cancer and Blood - West Des Moines Clinic

    Clive, Iowa, 50325

  • Kootenai Health - Coeur d'Alene

    Coeur d'Alene, Idaho, 83814

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • Rocky Mountain Cancer Centers-Penrose

    Colorado Springs, Colorado, 80907

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Bay Area Hospital

    Coos Bay, Oregon, 97420

  • Greater Regional Medical Center

    Creston, Iowa, 50801

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Essentia Health - Deer River Clinic

    Deer River, Minnesota, 56636

  • Northwestern Medicine Cancer Center Kishwaukee

    DeKalb, Illinois, 60115

  • AdventHealth Porter

    Denver, Colorado, 80210

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • UI Health Care Mission Cancer and Blood - Des Moines Clinic

    Des Moines, Iowa, 50309

  • Broadlawns Medical Center

    Des Moines, Iowa, 50314

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • UI Health Care Mission Cancer and Blood - Laurel Clinic

    Des Moines, Iowa, 50314

  • Iowa Lutheran Hospital

    Des Moines, Iowa, 50316

  • Henry Ford Health Saint John Hospital

    Detroit, Michigan, 48236

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • Essentia Health Saint Mary's Medical Center

    Duluth, Minnesota, 55805

  • Miller-Dwan Hospital

    Duluth, Minnesota, 55805

  • Pocono Medical Center

    East Stroudsburg, Pennsylvania, 18301

  • Marshfield Medical Center-EC Cancer Center

    Eau Claire, Wisconsin, 54701

  • Swedish Cancer Institute-Edmonds

    Edmonds, Washington, 98026

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • Illinois CancerCare-Eureka

    Eureka, Illinois, 61530

  • Providence Regional Cancer Partnership

    Everett, Washington, 98201

  • Parkland Health Center - Farmington

    Farmington, Missouri, 63640

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Holy Cross Hospital

    Fort Lauderdale, Florida, 33308

  • Mercy Hospital Fort Smith

    Fort Smith, Arkansas, 72903

  • Unity Hospital

    Fridley, Minnesota, 55432

  • Saint Luke's Cancer Institute - Fruitland

    Fruitland, Idaho, 83619

  • Gibbs Cancer Center-Gaffney

    Gaffney, South Carolina, 29341

  • Illinois CancerCare-Galesburg

    Galesburg, Illinois, 61401

  • Western Illinois Cancer Treatment Center

    Galesburg, Illinois, 61401

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • Nebraska Cancer Specialists/Oncology Hematology West PC

    Grand Island, Nebraska, 68803

  • Benefis Sletten Cancer Institute

    Great Falls, Montana, 59405

  • Great Falls Clinic

    Great Falls, Montana, 59405

  • Gibbs Cancer Center-Pelham

    Greer, South Carolina, 29651

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Essentia Health Hibbing Clinic

    Hibbing, Minnesota, 55746

  • Edward Hines Jr VA Hospital

    Hines, Illinois, 60141

  • CHI Saint Vincent Cancer Center Hot Springs

    Hot Springs, Arkansas, 71913

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Swedish Cancer Institute-Issaquah

    Issaquah, Washington, 98029

  • MU Health Care Goldschmidt Cancer Center

    Jefferson City, Missouri, 65109

  • Mercy Hospital Joplin

    Joplin, Missouri, 64804

  • Logan Health Medical Center

    Kalispell, Montana, 59901

  • CHI Health Good Samaritan

    Kearney, Nebraska, 68847

  • Illinois CancerCare-Kewanee Clinic

    Kewanee, Illinois, 61443

  • University of Tennessee - Knoxville

    Knoxville, Tennessee, 37920

  • Providence Regional Cancer System-Lacey

    Lacey, Washington, 98503

  • Northwestern Medicine Lake Forest Hospital

    Lake Forest, Illinois, 60045

  • Saint Anthony Hospital

    Lakewood, Colorado, 80228

  • University of Michigan Health - Sparrow Lansing

    Lansing, Michigan, 48912

  • Saint Joseph Radiation Oncology Resource Center

    Lexington, Kentucky, 40504

  • Saint Joseph Hospital East

    Lexington, Kentucky, 40509

  • AdventHealth Littleton

    Littleton, Colorado, 80122

  • Trinity Health Saint Mary Mercy Livonia Hospital

    Livonia, Michigan, 48154

  • Longmont United Hospital

    Longmont, Colorado, 80501

  • PeaceHealth Saint John Medical Center

    Longview, Washington, 98632

  • Jewish Hospital

    Louisville, Kentucky, 40202

  • Baptist Health Louisville

    Louisville, Kentucky, 40207

  • UofL Health Medical Center Northeast

    Louisville, Kentucky, 40245

  • Illinois CancerCare-Macomb

    Macomb, Illinois, 61455

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Sovah Health Martinsville

    Martinsville, Virginia, 24112

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Idaho Urologic Institute-Meridian

    Meridian, Idaho, 83642

  • Saint Luke's Cancer Institute - Meridian

    Meridian, Idaho, 83642

  • East Jefferson General Hospital

    Metairie, Louisiana, 70006

  • LSU Healthcare Network / Metairie Multi-Specialty Clinic

    Metairie, Louisiana, 70006

  • Mount Sinai Medical Center

    Miami Beach, Florida, 33140

  • Beebe South Coastal Health Campus

    Millville, Delaware, 19967

  • Marshfield Medical Center - Minocqua

    Minocqua, Wisconsin, 54548

  • Community Medical Center

    Missoula, Montana, 59804

  • SSM Health Good Samaritan

    Mount Vernon, Illinois, 62864

  • Saint Alphonsus Cancer Care Center-Nampa

    Nampa, Idaho, 83687

  • Saint Luke's Cancer Institute - Nampa

    Nampa, Idaho, 83687

  • Louisiana State University Health Science Center

    New Orleans, Louisiana, 70112

  • University Medical Center New Orleans

    New Orleans, Louisiana, 70112

  • Helen F Graham Cancer Center

    Newark, Delaware, 19713

  • Medical Oncology Hematology Consultants PA

    Newark, Delaware, 19713

  • Providence Newberg Medical Center

    Newberg, Oregon, 97132

  • Cancer Care Center of O'Fallon

    O'Fallon, Illinois, 62269

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Mercy Hospital Oklahoma City

    Oklahoma City, Oklahoma, 73120

  • Alegent Health Immanuel Medical Center

    Omaha, Nebraska, 68122

  • Alegent Health Bergan Mercy Medical Center

    Omaha, Nebraska, 68124

  • Alegent Health Lakeside Hospital

    Omaha, Nebraska, 68130

  • Creighton University Medical Center

    Omaha, Nebraska, 68131

  • Illinois CancerCare-Ottawa Clinic

    Ottawa, Illinois, 61350

  • VA Palo Alto Health Care System

    Palo Alto, California, 94304

  • AdventHealth Parker

    Parker, Colorado, 80138

  • Illinois CancerCare-Pekin

    Pekin, Illinois, 61554

  • OSF Saint Francis Radiation Oncology at Pekin

    Pekin, Illinois, 61554

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • OSF Saint Francis Radiation Oncology at Peoria Cancer Center

    Peoria, Illinois, 61615

  • Methodist Medical Center of Illinois

    Peoria, Illinois, 61636

  • OSF Saint Francis Medical Center

    Peoria, Illinois, 61637

  • Illinois CancerCare-Peru

    Peru, Illinois, 61354

  • Valley Radiation Oncology

    Peru, Illinois, 61354

  • Michigan Healthcare Professionals Pontiac

    Pontiac, Michigan, 48341

  • Trinity Health Saint Joseph Mercy Oakland Hospital

    Pontiac, Michigan, 48341

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Providence Saint Vincent Medical Center

    Portland, Oregon, 97225

  • Kootenai Clinic Cancer Services - Post Falls

    Post Falls, Idaho, 83854

  • Illinois CancerCare-Princeton

    Princeton, Illinois, 61356

  • Saint Mary Corwin Medical Center

    Pueblo, Colorado, 81004

  • Beebe Health Campus

    Rehoboth Beach, Delaware, 19971

  • Marshfield Medical Center-Rice Lake

    Rice Lake, Wisconsin, 54868

  • Mercy Clinic-Rolla-Cancer and Hematology

    Rolla, Missouri, 65401

  • Phelps Health Delbert Day Cancer Institute

    Rolla, Missouri, 65401

  • MyMichigan Medical Center Saginaw

    Saginaw, Michigan, 48601

  • Heartland Regional Medical Center

    Saint Joseph, Missouri, 64506

  • Sainte Genevieve County Memorial Hospital

    Sainte Genevieve, Missouri, 63670

  • Essentia Health Sandstone

    Sandstone, Minnesota, 55072

  • Swedish Medical Center-Ballard Campus

    Seattle, Washington, 98107

  • Swedish Medical Center-First Hill

    Seattle, Washington, 98122

  • PeaceHealth United General Medical Center

    Sedro-Woolley, Washington, 98284

  • Welch Cancer Center

    Sheridan, Wyoming, 82801

  • Saint Michael Cancer Center

    Silverdale, Washington, 98383

  • Spartanburg Medical Center

    Spartanburg, South Carolina, 29303

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62702

  • Springfield Clinic

    Springfield, Illinois, 62702

  • Springfield Memorial Hospital

    Springfield, Illinois, 62781

  • Mercy Hospital Springfield

    Springfield, Missouri, 65804

  • CoxHealth South Hospital

    Springfield, Missouri, 65807

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Mercy Hospital South

    St Louis, Missouri, 63128

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Missouri Baptist Medical Center

    St Louis, Missouri, 63131

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

  • Marshfield Medical Center-River Region at Stevens Point

    Stevens Point, Wisconsin, 54482

  • Missouri Baptist Sullivan Hospital

    Sullivan, Missouri, 63080

  • BJC Outpatient Center at Sunset Hills

    Sunset Hills, Missouri, 63127

  • Saint Luke's Cancer Institute - Twin Falls

    Twin Falls, Idaho, 83301

  • SMC Center for Hematology Oncology Union

    Union, South Carolina, 29379

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • The Carle Foundation Hospital

    Urbana, Illinois, 61801

  • PeaceHealth Southwest Medical Center

    Vancouver, Washington, 98664

  • Essentia Health Virginia Clinic

    Virginia, Minnesota, 55792

  • Providence Saint Mary Regional Cancer Center

    Walla Walla, Washington, 99362

  • Henry Ford Health Warren Hospital

    Warren, Michigan, 48093

  • Northwestern Medicine Cancer Center Warrenville

    Warrenville, Illinois, 60555

  • Sibley Memorial Hospital

    Washington D.C., District of Columbia, 20016

  • Methodist West Hospital

    West Des Moines, Iowa, 50266-7700

  • Mercy Medical Center-West Lakes

    West Des Moines, Iowa, 50266

  • Marshfield Medical Center - Weston

    Weston, Wisconsin, 54476

  • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

    Ypsilanti, Michigan, 48197

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About this study

Official title: Phase II Study of Bladder-SparIng ChemoradiatioN With Durvalumab in Clinical Stage III, Node PosItive BladdeR CancEr (INSPIRE)

This phase II trial studies the benefit of adding an immunotherapy drug called MEDI4736 (durvalumab) to standard chemotherapy and radiation therapy in treating bladder cancer which has spread to the lymph nodes. Drugs used in standard chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with durvalumab may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Giving chemotherapy and radiation therapy with the addition of durvalumab may work better in helping tumors respond to treatment compared to chemotherapy and radiation therapy alone. Patients with limited regional lymph node involvement may benefit from attempt at bladder preservation, and use of immunotherapy and systemic chemotherapy.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To compare the clinical complete response rate (cCR) after chemoradiotherapy (chemoRT) with or without durvalumab in node-positive bladder cancer patients.

SECONDARY OBJECTIVES:

  1. To compare the toxicity profile in both arms using the Common Terminology Criteria for Adverse Events (CTCAE).

II. To estimate the progression-free survival (PFS) in both arms. III. To estimate overall survival (OS) post randomization in both arms. IV. To estimate the bladder intact event free survival (BIEFS) in both arms. V. To estimate the metastasis free survival (MFS) in both arms. VI. To estimate bladder cancer specific survival in both arms. VII. To estimate the complete clinical response duration in both arms. VIII. To estimate salvage cystectomy rates in both arms.

EXPLORATORY OBJECTIVE:

  1. Planned subgroup analyses for clinical outcome (clinical complete response [CR] rate post chemoRT +/- durvalumab, MFS, OS, PFS) based on stratification factors.

TRANSLATIONAL OBJECTIVE:

  1. To collect and bank tumor tissue and blood specimens at pre-and post-treatment with chemoRT +/- durvalumab to determine predictive or prognostic markers.

OUTLINE:

STEP 1 - Randomization: Patients are randomized to 1 of 2 arms.

ARM C: Patients undergo radiation therapy for 6.5-8 weeks. Beginning 4 days before or after starting radiation therapy, patients receive durvalumab intravenously (IV) over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning 4 days before or after starting radiation therapy, patients also receive gemcitabine hydrochloride IV over 30-60 minutes twice a week (BIW) for 6 weeks; or cisplatin IV over 30-60 minutes once a week (QW) for 6 weeks; or mitomycin IV over 30 minutes on day 1 of radiation and fluorouracil IV continuous infusion on days 1-5 and 16-20 of radiation in the absence of disease progression or unacceptable toxicity. Patients also undergo bladder biopsy on study, cystoscopy on study and during follow-up, as well as computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial. Patients may also undergo tumor tissue and blood sample collection on study.

ARM D: Patients undergo radiation therapy for 6.5-8 weeks. Beginning 4 days before or after starting radiation therapy, patients also receive gemcitabine hydrochloride IV over 30-60 minutes BIW for 6 weeks; or cisplatin IV over 30-60 minutes QW for 6 weeks; or mitomycin IV over 30 minutes on day 1 of radiation and fluorouracil IV continuous infusion on days 1-5 and 16-20 of radiation in the absence of disease progression or unacceptable toxicity. Patients also undergo bladder biopsy on study, cystoscopy on study and during follow-up, as well as CT or MRI throughout the trial. Patients may also undergo tumor tissue and blood sample collection on study.

STEP 2 - Registration: Patients are assigned to 1 of 2 arms.

ARM E: Patients previously randomized to Arm C (chemoradiation and durvalumab) who achieve clinical CR or clinical benefit receive durvalumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bladder biopsy on study, cystoscopy on study and during follow-up, as well as CT or MRI throughout the trial. Patients may also undergo tumor tissue and blood sample collection on study.

ARM F: Patients previously randomized to Arm D (chemoradiation) who achieve clinical CR or clinical benefit undergo observation. Patients also undergo bladder biopsy on study, cystoscopy on study and during follow-up, as well as CT or MRI throughout the trial. Patients may also undergo tumor tissue and blood sample collection on study.

After completion of study treatment, patients are followed up every 12 weeks for 1 year, every 6 months for year 2, and then annually for years 3-4.

Being tested
Biopsy of Bladder, Biospecimen Collection, Cisplatin, Computed Tomography, Cystoscopy
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biopsy of BladderProcedure or surgery

    Also called Bladder Biopsy

    Undergo bladder biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo tumor tissue and blood sample collection

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Given IV

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • CystoscopyProcedure or surgery

    Also called CS

    Undergo cystoscopy

  • DurvalumabBiological

    Also called Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI 4736, MEDI-4736

    Given IV

  • FluorouracilDrug

    Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione

    Given IV

  • Gemcitabine HydrochlorideDrug

    Also called dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemcitabine HCI, Gemzar

    Given IV

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • MitomycinDrug

    Also called Ametycine, Jelmyto, MITO, Mito-C

    Given IV

  • Patient ObservationOther

    Also called Active Surveillance, deferred therapy, expectant management, Observation

    Undergo observation

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate

    Undergo radiation therapy

Study groups in NCT04216290
Study groupRoleWhat they receive
Step 1, Arm C (durvalumab, radiation therapy, chemotherapy)ExperimentalPatients undergo radiation therapy for 6.5-8 weeks. Beginning 4 days before or after starting radiation therapy, patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning 4 days before or after starting radiation therapy, patients also receive gemcitabine hydrochloride IV over 30-60 minutes BIW for 6 weeks; or cisplatin IV over 30-60 minutes QW for 6 weeks; or mitomycin IV over 30 minutes on day 1 of radiation and fluorouracil IV continuous infusion on days 1-5 and 16-20 of radiation in the absence of disease progression or unacceptable toxicity. Patients also undergo bladder biopsy on study, cystoscopy on study and during follow-up, as well as CT or MRI throughout the trial. Patients may also undergo tumor tissue and blood sample collection on study.
Receives: Procedure: Biopsy of Bladder; Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Procedure: Cystoscopy; Biological: Durvalumab; Drug: Fluorouracil; Drug: Gemcitabine Hydrochloride; Procedure: Magnetic Resonance Imaging; Drug: Mitomycin; Radiation: Radiation Therapy
Step 1, Arm D (radiation therapy, chemotherapy)Active comparatorPatients undergo radiation therapy for 6.5-8 weeks. Beginning 4 days before or after starting radiation therapy, patients also receive gemcitabine hydrochloride IV over 30-60 minutes BIW for 6 weeks; or cisplatin IV over 30-60 minutes QW for 6 weeks; or mitomycin IV over 30 minutes on day 1 of radiation and fluorouracil IV continuous infusion on days 1-5 and 16-20 of radiation in the absence of disease progression or unacceptable toxicity. Patients also undergo bladder biopsy on study, cystoscopy on study and during follow-up, as well as CT or MRI throughout the trial. Patients may also undergo tumor tissue and blood sample collection on study.
Receives: Procedure: Biopsy of Bladder; Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Procedure: Cystoscopy; Drug: Fluorouracil; Drug: Gemcitabine Hydrochloride; Procedure: Magnetic Resonance Imaging; Drug: Mitomycin; Radiation: Radiation Therapy
Step 2, Arm E (durvalumab)ExperimentalPatients previously randomized to Arm C (chemoradiation and durvalumab) who achieve clinical CR or clinical benefit receive durvalumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bladder biopsy on study, cystoscopy on study and during follow-up, as well as CT or MRI throughout the trial. Patients may also undergo tumor tissue and blood sample collection on study.
Receives: Procedure: Biopsy of Bladder; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Cystoscopy; Biological: Durvalumab; Procedure: Magnetic Resonance Imaging
Step 2, Arm F (observation)Active comparatorPatients previously randomized to Arm D (chemoradiation) who achieve clinical CR or clinical benefit undergo observation undergo observation. Patients also undergo bladder biopsy on study, cystoscopy on study and during follow-up, as well as CT or MRI throughout the trial. Patients may also undergo tumor tissue and blood sample collection on study.
Receives: Procedure: Biopsy of Bladder; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Cystoscopy; Procedure: Magnetic Resonance Imaging; Other: Patient Observation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinical complete response (CR)

    Defined as CR in bladder and nodes with no distant metastases. This study is designed to detect an improvement in clinical CR rate from 37.5% on the chemoradiation (chemoRT) arm to 62.5% on the chemoRT + durvalumab arm. Patients who receive any chemoRT +/- durvalumab will be included in the interim and final analyses. Those who are unevaluable post chemoRT +/- durvalumab, such as those patients who drop out before completing treatment post randomization or drop out prior to evaluation of first response or those patients who cannot get computed tomography scan and or cystoscopy to evaluate for response will be considered non-responders.

    Measured: Up to 4 years

Secondary outcomes (8)

  1. Metastasis-free survival

    Patients who are alive and metastasis-free will be censored at date of last assessment. The Kaplan-Meier method will be used to estimate time-to-event endpoints and stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients.

    Measured: From randomization to first evidence of metastatic disease or death from any cause, assessed up to 4 years

  2. Bladder-intact event-free survival (BI-EFS)

    Events of interest are presence of muscle-invasive bladder cancer, clinical evidence of progression of nodal involvement or development of metastatic disease, radical cystectomy, or death due to any cause. Patients last known to be BI-EFS event-free will be censored at the date of last assessment. Patients alive without disease assessment will be censored at randomization. The Kaplan-Meier method will be used to estimate time-to-event endpoints and stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients.

    Measured: From randomization to the first BI-EFS event, assessed up to 4 years

  3. Bladder cancer specific survival

    Deaths due to other causes will be considered competing events and patients known to be alive will be censored at the date of last contact. The Kaplan-Meier method will be used to estimate time-to-event endpoints and stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients.

    Measured: From randomization to death from bladder cancer, assessed up to 4 years

  4. Overall survival

    Patients still alive will be censored at date of last contact. The Kaplan-Meier method will be used to estimate time-to-event endpoints and stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients.

    Measured: From randomization to death from any cause, assessed up to 4 years

  5. Progression-free survival

    Patients last known to be alive and progression-free will be censored at the date of last contact. The Kaplan-Meier method will be used to estimate time-to-event endpoints and stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients.

    Measured: From randomization to first of local progression, nodal or distant metastasis, or death from any cause, assessed up to 4 years

  6. Complete response duration

    Patients will be censored at the date of last disease assessment. The Kaplan-Meier method will be used to estimate time-to-event endpoints and stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients.

    Measured: From the date of the biopsy documenting the complete response to the time of muscle invasive recurrence, local progression, evidence of metastatic disease or death due to any cause, assessed up to 4 years

  7. Salvage cystectomy rate

    Will be reported as a proportion of patients who do not experience clinical benefit and undergo salvage cystectomy after chemoRT +/- durvalumab along with a 90% confidence interval. The Kaplan-Meier method will be used to estimate time-to-event endpoints and stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients.

    Measured: Up to 4 years

  8. Incidence of adverse events

    Assessed using the Common Terminology Criteria for Adverse Events version 5.0. Toxicity will be evaluated in all treated patients, regardless of eligibility.

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jan 2020
  2. Study start17 Mar 2021
  3. Primary completion4 Feb 2026
  4. Study completion19 May 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04216290
Sponsor's protocol ID
NCI-2019-08628
Other IDs
NCI-2019-08628, EA8185, EA8185, U10CA180820
Status last verified
May 2026
First submitted
31 Dec 2019
Last updated
22 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biopsy of Bladder, Biospecimen Collection and Cisplatin in people with Bladder Urothelial Carcinoma and Stage III Bladder Cancer AJCC v8, run by National Cancer Institute (NCI) at 216 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 70 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 216 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical complete response (CR) (time frame: Up to 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04216290.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.

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